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Chapter 12 - Antiepileptogenic Therapies for Post-traumatic Epilepsy: Is There Any Evidence?

Published online by Cambridge University Press:  10 August 2021

By
Francesco Brigo  and
Simona Lattanzi
Edited by
Marco Mula
Marco Mula
Affiliation:
St George's Hospital Medical School, University of London
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Summary

The use of antiepileptic drugs (AEDs) is effective in reducing the risk of developing early (acute symptomatic) post-traumatic seizures compared to placebo or usual care in patients with severe TBI (low-quality evidence). With regards to the choice of the AED, the available evidence supports the use of phenytoin, starting with an intravenous loading dose initiated as soon as possible after severe TBI]. Despite the lack of evidence from comparative clinical trials, levetiracetam is increasingly used in primary prevention of early post-traumatic seizures due to its ease of use, favorable safety profile and lack of pharmacokinetic interactions. So far, there is no evidence to support the use of other neuroprotective agents for the primary prevention of early post-traumatic seizures. Patients with early post-traumatic seizures do not generally require long-term AED treatment since their risk to develop post-traumatic epilepsy is low. High-quality and adequately powered trials conducted in a selected population at high risk of developing late post-traumatic seizures are required to draw definite conclusions on the effectiveness of long-term prophylactic treatment. Further studies to explore the antiepileptogenic and neuroprotective effects of anti-inflammatory and immune-modulatory therapies are also warranted.

Keywords

AntiepileptogenesisAntiepileptic drugsPhenytoinRandomized controlled trialsPrimary preventionPost-traumatic epilepsy
Type
Chapter
Information
Post-traumatic Epilepsy , pp. 157 - 168
Publisher: Cambridge University Press
Print publication year: 2021

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References

Frey, LC. Epidemiology of posttraumatic epilepsy: a critical review. Epilepsia 2003;44:11–17.Google Scholar
Agrawal, A, Timothy, J, Pandit, L, Manju, M. Post-traumatic epilepsy: an overview. Clin Neurol Neurosurg 2006;108:433–9.CrossRefGoogle ScholarPubMed
Scheffer, IE, Berkovic, S, Capovilla, G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017;58:512–21.CrossRefGoogle ScholarPubMed
Annegers, JF, Hauser, WA, Coan, SP, Rocca, WA. A population-based study of seizures after traumatic brain injuries. N Engl J Med 1998;338:20–4.Google Scholar
Pitkänen, A, McIntosh, TK. Animal models of post-traumatic epilepsy. J Neurotrauma 2006;23:241–61CrossRefGoogle ScholarPubMed
Pitkänen, A, Bolkvadze, T, Immonen, R. Anti-epileptogenesis in rodent post-traumatic epilepsy models. Neurosci Lett 2011;497:163–71.CrossRefGoogle ScholarPubMed
Pitkänen, A, Immonen, R. Epilepsy related to traumatic brain injury. Neurotherapeutics 2014;11:286–96.Google Scholar
Fisher, RS, Acevedo, C, Arzimanoglou, A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014;55:475–82.CrossRefGoogle ScholarPubMed
Beghi, E, Carpio, A, Forsgren, L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia 2010;51:671–5.CrossRefGoogle ScholarPubMed
Hesdorffer, DC, Benn, EK, Cascino, GD, Hauser, WA. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia 2009;50:1102–8.CrossRefGoogle ScholarPubMed
Fisher, RS, van Emde Boas, W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46:470–2.Google ScholarPubMed
Haltiner, AM, Temkin, NR, Dikmen, SS. Risk of seizure recurrence after the first late posttraumatic seizure. Arch Phys Med Rehabil 1997;78:835–40.Google Scholar
Pitkänen, A, Kharatishvili, I, Karhunen, H, et al. Epileptogenesis in experimental models. Epilepsia 2007;48:13–20Google Scholar
Webster, KM, Sun, M, Crack, P, O’Brien, TJ, Shultz, SR, Semple, BD. Inflammation in epileptogenesis after traumatic brain injury. J Neuroinflammation 2017;14:10.CrossRefGoogle ScholarPubMed
Cotter, D, Kelso, A, Neligan, A. Genetic biomarkers of posttraumatic epilepsy: A systematic review. Seizure 2017;46:53–8.CrossRefGoogle ScholarPubMed
Trinka, E, Brigo, F. Antiepileptogenesis in humans: disappointing clinical evidence and ways to move forward. Curr Opin Neurol 2014;27:227–35.Google Scholar
Mani, R, Pollard, J, Dichter, MA. Human clinical trials in antiepileptogenesis. Neurosci Lett 2011; 497 :251–6.Google Scholar
Schmidt, D. Is antiepileptogenesis a realistic goal in clinical trials? Concerns and new horizons. Epileptic Disord 2012;14:105–13.Google Scholar
Jr, Engel J, Pitkänen, A, Loeb, JA, et al. Epilepsy biomarkers. Epilepsia 2013;54:61–9.Google Scholar
Ritter, AC, Wagner, AK, Szaflarski, JP, et al. Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury. Epilepsia 2016;57:1503–14.CrossRefGoogle ScholarPubMed
Bakr, A, Belli, A. A systematic review of levetiracetam versus phenytoin in the prevention of late post-traumatic seizures and survey of UK neurosurgical prescribing practice of antiepileptic medication in acute traumatic brain injury. Br J Neurosurg 2018;32:237–44.Google Scholar
Thompson, K, Pohlmann-Eden, B, Campbell, LA, Abel, H. Pharmacological treatments for preventing epilepsy following traumatic head injury. Cochrane Database Syst Rev. 2015;CD009900.Google Scholar
Glotzner, FL, Haubitz, I, Miltner, F, Kapp, G, Pflughaupt, KW. Seizure prevention using carbamazepine following severe brain injuries [Anfallsprophylaxe mit Carbamazepin nach schweren Schadelhirnverletzungen Neurochirurgia 1983;26:66–79.Google Scholar
Young, B, Rapp, RP, Norton, JA, Haack, D, Tibbs, PA, Bean, JR. Failure of prophylactically administered phenytoin to prevent late posttraumatic seizures. J Neurosurg 1983;58:236–41.Google Scholar
Temkin, NR, Dikmen, SS, Wilensky, AJ, Keihm, J, Chabal, S, Winn, HR. A randomized double-blind study of phenytoin for the prevention of post-traumatic seizures. N Eng J Med 1990;323:497–502.Google Scholar
Pechadre, JC, Lauxerois, M, Colnet, G, et al. Prevention of late posttraumatic epilepsy by phenytoin in severe brain injuries, 2 years’ follow-up [Prevention de l’epilepsie post–traumatique tardive par phenytoine dans les traumatismes crannies graves, suivi durant 2 ans Presse Medicale 1991;20:841–5.Google ScholarPubMed
Young, KD, Okada, PJ, Sokolove, PE, et al. A randomized, double-blinded, placebo-controlled trial of phenytoin for the prevention of early posttraumatic seizures in children with moderate to severe blunt head injury. Ann Emerg Med 2004;43:435–46.Google Scholar
Temkin, NR, Anderson, GC, Winn, HR, et al. Magnesium sulfate for neuroprotection after traumatic brain injury: a randomized controlled trial. Lancet Neurol 2007;6:29–38.Google Scholar
Temkin, NR, Dikmen, SS, Anderson, GD, et al. Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg 1999;91:593–600.Google Scholar
Szaflarski, JP, Sangha, KS, Lindsell, CJ, Shutter, LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care 2010;12:165–72.Google Scholar
McQueen, JK, Blackwood, DHR, Harris, P, Kalbag, RM, Johnson, AL. Low risk of late post-traumatic seizures following severe head injury: implications for clinical trials of prophylaxis. J Neurol Neurosurg Psychiatr 1983;46:899–904.CrossRefGoogle ScholarPubMed
Manaka, S. Cooperative prospective study on posttraumatic epilepsy: risk factors and the effect of prophylactic anticonvulsant. Japan J Psychiatr Neurol 1992;46:311–5.Google Scholar
Yang, Y, Zheng, F, Xu, X, Wang, X. Levetiracetam versus phenytoin for seizure prophylaxis following traumatic brain injury: A systematic review and meta-analysis. CNS Drugs. 2016;30:677–88.Google Scholar
Beghi, E. Overview of studies to prevent posttraumatic epilepsy. Epilepsia 2003;44:21–6.Google Scholar
Chang, BS, Lowenstein, DH. Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2003; 60:10–16.Google Scholar
Carney, N, Totten, AM, O’Reilly, C, et al. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017;80:6–15.Google Scholar
Cotton, BA, Kao, LS, Kozar, R, Holcomb, JB. Cost-utility analysis of levetiracetam and phenytoin for posttraumatic seizure prophylaxis. J Trauma 2011;71:375–9.Google Scholar
Inaba, K, Menaker, J, Branco, BC, et al. A prospective multicenter comparison of levetiracetam versus phenytoin for early posttraumatic seizure prophylaxis. J Trauma Acute Care Surg. 2013;74:766–71Google Scholar
Zaccara, G, Perucca, E. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs. Epileptic Disord 2014;16:409–31.Google Scholar
Shohrati, M, Rouini, MR, Mojtahedzadeh, M, Firouzabadi, M. Evaluation of phenytoin pharmacokinetics in neurotrauma patients. Daru 2007;15:34–40.Google Scholar
Sadeghi, K, Hadi, F, Ahmadi, A, et al. Total phenytoin concentration is not well correlated with active free drug in critically-ill head trauma patients. J Res Pharm Pract 2013;2:105–9Google Scholar
Alimardani, S, Sadrai, S, Masoumi, HT, et al. Pharmacokinetic behavior of phenytoin in head trauma and cerebrovascular accident patients in an Iranian population. J Res Pharm Pract. 2017;6:217–22.Google Scholar
Kruer, RM, Harris, LH, Goodwin, H, et al. Changing trends in the use of seizure prophylaxis after traumatic brain injury: a shift from phenytoin to levetiracetam. J Crit Care 2013;28:883.e9–13CrossRefGoogle ScholarPubMed
Szaflarski, JP. Is there equipoise between phenytoin and levetiracetam for seizure prevention in traumatic brain injury? Epilepsy Curr 2015;15:94–7.Google Scholar

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